Dual PCSK9 Inhibition With Inclisiran and Alirocumab in Secondary Prevention

ConditionsHypercholesterolemia Atherosclerotic Cardiovascular Disease (ASCVD)

Trial statusRecruiting

Trial phasePhase 4

Trial typeInterventional

Biological sexAll

Age18+

SponsorUniversity Medical Centre Ljubljana

About this trial

This study will evaluate the effectiveness and safety of combining two different types of PCSK9 inhibitors, inclisiran and alirocumab, in patients with high cardiovascular risk who are unable to tolerate statins.

Lowering low-density lipoprotein cholesterol (LDL-C) is essential to reduce the risk of cardiovascular events. While PCSK9 inhibitors are effective, many patients treated with a single agent do not reach recommended LDL-C targets, especially those who cannot take statins.

Inclisiran and alirocumab reduce LDL-C through different mechanisms. Inclisiran decreases the production of PCSK9 in the liver, while alirocumab binds circulating PCSK9 in the blood. Combining these therapies may lead to a greater reduction in LDL-C levels.

In this randomized, open-label clinical trial, approximately 60 patients in secondary prevention will be assigned to one of three groups: inclisiran alone, alirocumab alone, or a combination of both treatments. Patients will be followed for 9 months with regular clinical and laboratory assessments.

The main goal of the study is to determine whether combination therapy leads to greater LDL-C reduction compared to each treatment alone. Secondary objectives include assessing the proportion of patients achieving target LDL-C levels and evaluating treatment safety and tolerability.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Adults aged ≥18 years

Established atherosclerotic cardiovascular disease (secondary prevention), defined as prior cardiovascular events or imaging-confirmed atherosclerosis (e.g., coronary artery disease on angiography or CT, carotid plaque on ultrasound, or peripheral arterial disease).

Eligible for PCSK9 inhibitor therapy according to national clinical criteria

Fasting LDL cholesterol ≥2.5 mmol/L and ≤5.0 mmol/L at screening

Disqualifiers

Eligibility for PCSK9 inhibitor therapy solely based on elevated lipoprotein(a) >1000 mg/L with LDL-C below inclusion threshold

Prior use of any PCSK9 inhibitor (alirocumab, evolocumab or inclisiran) before enrollment

Planned initiation or modification of lipid-lowering therapy during the study period

Known homozygous familial hypercholesterolemia

Trial design

Design model

Parallel

Treatments tested in this trial

Inclisiran
Drug
Participants receive inclisiran 284 mg administered subcutaneously at baseline (Day 0) and at Month 3.
Alirocumab
Drug
Participants receive alirocumab 300 mg administered subcutaneously every four weeks in a supervised clinical setting for 9 months.

Treatment groups

60 Participants

are divided into 3 treatment groups

Group A: InclisiranExperimental treatment 1 intervention

Group B: AlirocumabExperimental treatment 1 intervention

Group C: Inclisiran Plus AlirocumabExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

Percent Change in LDL-C From Baseline

Percent change in low-density lipoprotein cholesterol (LDL-C) from baseline at 3 months and 9 months, comparing inclisiran, alirocumab, and combination therapy.

Time frame

3 months and 9 months

Secondary outcomes

Trajectory of Percent Change in LDL-C From Baseline

Percent change in LDL-C from baseline at each scheduled follow-up visit to assess early response and durability of treatment effect.

Time frame

1, 3, 6, and 9 months

Change From Baseline in LDL-C Concentration

Absolute change in LDL-C concentration compared with baseline at each scheduled follow-up visit.

Time frame

1, 3, 6, and 9 months

Proportion of Participants Achieving LDL-C <1.4 mmol/L

Proportion of participants achieving LDL-C below 1.4 mmol/L at each scheduled follow-up visit.

Time frame

1, 3, 6, and 9 months

Change in Apolipoprotein B From Baseline

Absolute and percent change in apolipoprotein B from baseline.

Time frame

1, 3, 6, and 9 months

Other outcomes

Incidence of Injection-Site Reactions

Number and proportion of participants experiencing injection-site reactions.

Time frame

Up to 9 months

Treatment Adherence

Adherence to assigned therapy assessed by documented administration of inclisiran and alirocumab.

Time frame

Up to 9 months

Major Adverse Cardiovascular Events

Exploratory assessment of cardiovascular death, myocardial infarction, stroke, urgent coronary revascularization, or hospitalization for unstable angina.

Time frame

Up to 9 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University Medical Centre Ljubljana

Lead sponsor

Source ClinicalTrials.gov

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